tbuckley/cabot-search huggingface dataset:
Psychiatric morbidity in dermatological outpatients: an issue to be recognized
Authors: A. Picardi, D. Abeni, C.F. Melchi, P. Puddu, P. Pasquini
Journal: British Journal of Dermatology (2000)

Background There is a high prevalence of psychiatric disorders in dermatological outpatients. Objectives To estimate the magnitude of this problem and to identify a set of variables associated with the presence of psychiatric disorder. Methods All adults attending the outpatient clinics of a dermatological hospital on predetermined days were given a questionnaire comprising the Skindex‐29 and the 12‐item General Health Questionnaire (GHQ‐12). Results In total, 4268 questionnaires were given at admission, and 3125 were returned. Of these, 546 were blank or incomplete, leaving 2579 respondents (response rate 60·4%). Using a stringent cut‐off threshold (≥ 5) for psychiatric case identification with the GHQ‐12, scored in the conventional way, the overall prevalence of psychiatric morbidity was 25·2% (95% confidence interval 23·6–27·0%). We found a higher prevalence of psychiatric disorders in women and in widows/widowers, controlling for age. Health‐related quality of life was a much stronger predictor of psychiatric morbidity than physician‐rated clinical severity. High prevalence rates (> 30%) were observed among patients with acne, pruritus, urticaria, alopecia and herpesvirus infections, and in subjects without objective signs of dermatological disease. Conclusions Our study has depicted the situation that is actually faced by dermatologists in their everyday practice, where they are in a unique position to recognize psychiatric morbidity and to take appropriate measures. The GHQ‐12, being easy for patients to compile and for physicians or nurses to score, may be a practical tool to increase identification of patients with substantial psychological distress or formal psychiatric disorder in order to provide more comprehensive and appropriate intervention.
Industry Sponsorship and Financial Conflict of Interest in the Reporting of Clinical Trials in Psychiatry
Authors: Roy H. Perlis, Clifford S. Perlis, Yelena Wu, Cindy Hwang, Megan Joseph, Andrew A. Nierenberg
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Financial conflict of interest has been reported to be prevalent in clinical trials in general medicine and associated with a greater likelihood of reporting results favorable to the intervention being studied. The extent and implications of industry sponsorship and financial conflict of interest in psychiatric clinical trials have not been investigated, to the authors’ knowledge. METHOD: The authors examined funding source and author financial conflict of interest in all clinical trials published in the American Journal of Psychiatry, the Archives of General Psychiatry, the Journal of Clinical Psychopharmacology, and the Journal of Clinical Psychiatry between 2001 and 2003. RESULTS: Among 397 clinical trials identified, 239 (60%) reported receiving funding from a pharmaceutical company or other interested party, and 187 studies (47%) included at least one author with a reported financial conflict of interest. Among the 162 randomized, double-blind, placebo-controlled studies examined, those that reported conflict of interest were 4.9 times more likely to report positive results; this association was significant only among the subset of pharmaceutical industry-funded studies. CONCLUSIONS: Author conflict of interest appears to be prevalent among psychiatric clinical trials and to be associated with a greater likelihood of reporting a drug to be superior to placebo.
Clinical Trial Results of a HER2/<i>neu</i> (E75) Vaccine to Prevent Recurrence in High-Risk Breast Cancer Patients
Authors: George E. Peoples, Jennifer M. Gurney, Matthew T. Hueman, Mike M. Woll, Gayle B. Ryan, Catherine E. Storrer, Christine Fisher, Craig D. Shriver, Constantin G. Ioannides, Sathibalan Ponniah
Journal: Journal of Clinical Oncology (2005)

Purpose E75 is an immunogenic peptide from the HER2/neu protein that is highly expressed in breast cancer. We are conducting a clinical trial of an E75 + granulocyte-macrophage colony-stimulating factor vaccine to assess safety, immunologic response, and the prevention of clinical recurrences in patients with disease-free, node-positive breast cancer (NPBC). Patients and Methods Fifty-three patients with NPBC were enrolled and HLA typed. HLA-A2 + patients (n = 24) were vaccinated, and HLA-A2 − patients (n = 29) are observed prospectively as clinical controls. Local/systemic toxicities, immunologic responses, and time to recurrence are being measured. Results Only minor toxicities have occurred (one grade 3 [4%]). All patients have demonstrated clonal expansion of E75-specific CD8 + T cells that lysed HER2/neu-expressing tumor cells. An optimal dosage and schedule have been established. Patients have developed delayed-type hypersensitivity reactions to E75 postvaccination compared with controls (33 v 7 mm; P &lt; .01). HLA-A2 + patients have been found to have larger, more poorly differentiated, and more hormonally insensitive tumors compared to HLA-A2 − patients. Despite this, the only two deaths have occurred in the control group. The disease-free survival in the vaccinated group is 85.7% compared to 59.8% in the controls at 22 months' median follow-up with a recurrence rate of 8% compared to 21%, respectively (P &lt; .19). Median time to recurrence in the vaccinated patients was prolonged (11 v 8 months), and recurrence correlated with a weak delayed-type hypersensitivity response. Conclusion This HER2/neu (E75) vaccine is safe and effective in eliciting a peptide-specific immune response in vivo. Induced HER2/neu immunity seems to reduce the recurrence rate in patients with NPBC.
DNA Sequencing versus Standard Prenatal Aneuploidy Screening
Authors: Diana W. Bianchi, R. Lamar Parker, Jeffrey Wentworth, Rajeevi Madankumar, Craig Saffer, Anita F. Das, Joseph A. Craig, Darya I. Chudova, Patricia L. Devers, Keith W. Jones, Kelly Oliver, Richard P. Rava, Amy J. Sehnert
Journal: New England Journal of Medicine (2014)

In high-risk pregnant women, noninvasive prenatal testing with the use of massively parallel sequencing of maternal plasma cell-free DNA (cfDNA testing) accurately detects fetal autosomal aneuploidy. Its performance in low-risk women is unclear.
Risk of Upper and Lower Gastrointestinal Bleeding in Patients Taking Nonsteroidal Anti-inflammatory Drugs, Antiplatelet Agents, or Anticoagulants
Authors: Ángel Lanas, Patricia Carrera-Lasfuentes, Yolanda Arguedas, Santiago García, Luis Bujanda, Xavier Calvet, Julio Ponce, Ángeles Perez-Aísa, Manuel Castro, Maria Muñoz, Carlos Sostres, Luis A. García-Rodríguez
Journal: Clinical Gastroenterology and Hepatology (2014)
Fertility Preservation in Breast Cancer Patients: A Prospective Controlled Comparison of Ovarian Stimulation With Tamoxifen and Letrozole for Embryo Cryopreservation
Authors: Kutluk Oktay, Erkan Buyuk, Natalie Libertella, Munire Akar, Zev Rosenwaks
Journal: Journal of Clinical Oncology (2005)

Purpose To develop safe ovarian stimulation methods to perform in vitro fertilization (IVF) in breast cancer patients who wish to preserve their fertility via embryo cryopreservation before chemotherapy. Patients and Methods Sixty women (age range, 24 to 43 years) with breast cancer were prospectively studied. Twenty-nine patients underwent 33 ovarian stimulation cycles with either tamoxifen 60 mg/d alone (Tam-IVF) or in combination with low-dose follicle-stimulating hormone (TamFSH-IVF) or letrozole 5 mg in combination with FSH (Letrozole-IVF). After IVF, all resultant embryos were cryopreserved to preserve fertility. Recurrence rates were compared with controls (n = 31) who elected not to undergo IVF. Results Compared with Tam-IVF, both TamFSH-IVF and Letrozole-IVF patients had greater numbers of follicles (2 ± 0.3 v 6 ± 1 and 7.8 ± 0.9, respectively; P &lt; .0001), mature oocytes (1.5 ± 0.3 v 5.1 ± 1.1 and 8.5 ± 1.6, respectively; P &lt; .001), and embryos (1.3 ± 0.2 v 3.8 ± 0.8 and 5.3 ± 0.8, respectively; P &lt; .001). Peak estradiol (E 2 ) levels were lower with Letrozole-IVF and Tam-IVF compared with TamFSH-IVF. After 554 ± 31 days (range, 153 to 1,441 days) of follow-up, cancer recurrence rate was similar between IVF and control patients (three of 29 v three of 31 patients, respectively; hazard ratio, 1.5; 95% CI, 0.29 to 7.4), and this estimate was not affected by cancer stage. Conclusion The combination of low-dose FSH with tamoxifen (TamFSH-IVF) or letrozole (Letrozole-IVF) results in higher embryo yield compared with Tam-IVF. Recurrence rates do not seem to be increased, but the letrozole protocol may be preferred because it results in lower peak E 2 levels.
Cardiac Resynchronization in Chronic Heart Failure
Authors: William T. Abraham, Westby G. Fisher, Andrew L. Smith, David B. Delurgio, Angel R. Leon, Evan Loh, Dusan Z. Kocovic, Milton Packer, Alfredo L. Clavell, David L. Hayes, Myrvin Ellestad, Robin J. Trupp, Jackie Underwood, Faith Pickering, Cindy Truex, Peggy McAtee, John Messenger
Journal: New England Journal of Medicine (2002)

Previous studies have suggested that cardiac resynchronization achieved through atrial-synchronized biventricular pacing produces clinical benefits in patients with heart failure who have an intraventricular conduction delay. We conducted a double-blind trial to evaluate this therapeutic approach.
Permanent Coverage of Large Burn Wounds with Autologous Cultured Human Epithelium
Authors: G. Gregory Gallico, Nicholas E. O'Connor, Carolyn C. Compton, Olaniyi Kehinde, Howard Green
Journal: New England Journal of Medicine (1984)

WHEN burns are so extensive that skin grafts obtainable from remaining donor sites are insufficient to provide wound coverage, a new source of autograft must be found. Human epidermal cells from a small skin-biopsy sample can be cultured to produce coherent epithelial sheets sufficient to cover the entire body surface.1,2 When this epithelium was applied to wounds on athymic mice it generated a human epidermis.3 Autologous cultured epithelium placed on small burn wounds in adults'1 and children5 adhered and generated a permanent epidermis similar to that resulting from split-thickness skin grafts. We report here that in two children who sustained . . .
Tacrolimus ointment is more effective than pimecrolimus cream with a similar safety profile in the treatment of atopic dermatitis: Results from 3 randomized, comparative studies
Authors: Amy S. Paller, Mark Lebwohl, Alan B. Fleischer, Richard Antaya, Richard G. Langley, Robert S. Kirsner, Robin R. Blum, M. Joyce Rico, Eileen Jaracz, Andrew Crowe, Gregory J. Linowski
Journal: Journal of the American Academy of Dermatology (2005)
Effects of PKF275-055, a dipeptidyl peptidase–4 inhibitor, on the development of atherosclerotic lesions in apolipoprotein E–null mice
Authors: Michishige Terasaki, Masaharu Nagashima, Takuya Watanabe, Kyoko Nohtomi, Yusaku Mori, Akira Miyazaki, Tsutomu Hirano
Journal: Metabolism (2012)
Early Inhaled Nitric Oxide Therapy in Premature Newborns with Respiratory Failure
Authors: John P. Kinsella, Gary R. Cutter, William F. Walsh, Dale R. Gerstmann, Carl L. Bose, Claudia Hart, Kris C. Sekar, Richard L. Auten, Vinod K. Bhutani, Jeffrey S. Gerdes, Thomas N. George, W. Michael Southgate, Heather Carriedo, Robert J. Couser, Mark C. Mammel, David C. Hall, Mariann Pappagallo, Smeeta Sardesai, John D. Strain, Monika Baier, Steven H. Abman
Journal: New England Journal of Medicine (2006)

The safety and efficacy of early, low-dose, prolonged therapy with inhaled nitric oxide in premature newborns with respiratory failure are uncertain.
Outcomes and Prognostic Factors in Critically Ill Patients with Hematologic Malignancies Admitted in an Intensive Care Unit: A Single Center Experience. Hospital De Clínicas, Montevideo, Uruguay
Authors: Carolina Oliver, Adriana Peixoto, Cecilia Guillermo, Juan Zunino, Mariana Stevenazzi, Alberto Biestro, Lilian Diaz
Journal: Blood (2014)
The Effect of Ethnicity on Physician Estimates of Pain Severity in Patients With Isolated Extremity Trauma
Authors: Knox H. Todd
Journal: JAMA (1994)

<h3>Objective.</h3> —To determine whether physician estimates of pain severity are influenced by patient ethnicity. <h3>Design.</h3> —Prospective cohort study. <h3>Setting.</h3> —UCLA Emergency Medicine Center, a level I trauma center, Los Angeles, Calif. <h3>Participants.</h3> —Hispanic and non-Hispanic white patients presenting to the emergency department with extremity trauma when research assistants were present. Exclusion criteria were patient refusal, altered mentation, or severe injury interfering with the interview process. <h3>Main Outcome Measures.</h3> —The difference between patient and physician estimates of pain severity as assessed on a visual analog scale for Hispanics and non-Hispanic whites. <h3>Results.</h3> —A total of 138 non-Hispanic white and 69 Hispanic patients participated in the study. The groups differed in language use, insurance status, and proportions suffering occupational injury. There were no differences between non-Hispanic white and Hispanic patients in patient pain assessments (mean, 39.8 mm vs 39.0 mm, respectively;<i>P</i>=.86), physician pain assessments (mean, 33.6 mm vs 29.7 mm;<i>P</i>=.23), or the disparity between patient and physician pain assessments (mean 6.1 mm vs 9.4 mm;<i>P</i>=.38). The degree of disparity between patient and physician pain assessments remained similar for both groups even after controlling for multiple potential confounders. <h3>Conclusions.</h3> —Physician ability to assess pain severity does not differ for Hispanic and non-Hispanic white patients. Other explanations for a difference in analgesic practice as a function of ethnicity should be explored. (<i>JAMA</i>. 1994;271:925-928)
Increased Expression of Interleukin-1β and Monocyte Chemotactic and Activating Factor/Monocyte Chemoattractant Protein-1 in the Hypertrophied and Failing Heart With Pressure Overload
Authors: Tetsuo Shioi, Akira Matsumori, Yasuki Kihara, Moriaki Inoko, Koh Ono, Yoshitaka Iwanaga, Takehiko Yamada, Atsushi Iwasaki, Kouji Matsushima, Shigetake Sasayama
Journal: Circulation Research (1997)

Abstract Studies on the effects of proinflammatory cytokines on the heart suggest that they play some roles in the pathogenesis of congestive heart failure (CHF). To determine the involvement of proinflammatory cytokine in cardiac hypertrophy and CHF induced by mechanical overload, we investigated the expression of interleukin (IL)-1β and monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein-1 (MCP-1) in the left ventricle (LV) of Dahl salt-sensitive (DS) rats that showed hypertrophy of the LV induced by hypertension and subsequently developed CHF. The IL-1β mRNA content in the LV of DS rats increased 3.9-fold when LV hypertrophy developed, and the increase reached 6.2-fold at the CHF stage compared with that of age-matched Dahl salt-resistant (DR) rats. The amount of IL-1β in the LV was positively correlated with the LV weight/body weight ratio. Most of the IL-1β immunoreactivity was localized in the endothelial cells and interstitial macrophages. The mRNA levels of MCAF in the LV increased 3.6-fold at 11 weeks and reached 4.8-fold at the CHF stage relative to the age-matched DR rats. MCAF protein was localized to the endothelial cells and interstitial macrophages. In DS rats, the number of interstitial macrophages increased diffusely throughout the LV. We suggest that increased chemokine expression, macrophage infiltration, and proinflammatory cytokine expression play some role in the pathogenesis of cardiac hypertrophy and failure induced by chronic mechanical overload.
The suppression of cervical cancer ferroptosis by macrophages: The attenuation of ALOX15 in cancer cells by macrophages-derived exosomes
Authors: Yanlin Luo, Yibing Chen, Huan Jin, Benxin Hou, Hongsheng Li, Xiang Li, Lingfeng Liu, Yuan Zhou, Yonghua Li, Yong Sang Song, Quentin Liu, Zhengzhi Zou
Journal: Acta Pharmaceutica Sinica B (2023)

Induction of cancer cell ferroptosis has been proposed as a potential treatment in several cancer types. Tumor-associated macrophages (TAMs) play a key role in promoting tumor malignant progression and therapy resistance. However, the roles and mechanisms of TAMs in regulating tumor ferroptosis is still unexplored and remains enigmatic. This study shows ferroptosis inducers has shown therapeutic outcomes in cervical cancer in vitro and in vivo. TAMs have been found to suppress cervical cancer cells ferroptosis. Mechanistically, macrophage-derived miRNA-660-5p packaged into exosomes are transported into cancer cells. In cancer cells, miRNA-660-5p attenuates ALOX15 expression to inhibit ferroptosis. Moreover, the upregulation of miRNA-660-5p in macrophages depends on autocrine IL4/IL13-activated STAT6 pathway. Importantly, in clinical cervical cancer cases, ALOX15 is negatively associated with macrophages infiltration, which also raises the possibility that macrophages reduce ALOX15 levels in cervical cancer. Moreover, both univariate and multivariate Cox analyses show ALOX15 expression is independent prognostic factor and positively associated with good prognosis in cervical cancer. Altogether, this study reveals the potential utility of targeting TAMs in ferroptosis-based treatment and ALOX15 as prognosis indicators for cervical cancer.
Dose and Dose Intensity of Adjuvant Chemotherapy for Stage II, Node-Positive Breast Carcinoma
Authors: William C. Wood, Daniel R. Budman, Ann H. Korzun, M. Robert Cooper, Jerry Younger, Ronald D. Hart, Anne Moore, John A. Ellerton, Larry Norton, Carolyn R. Ferree, Anita Colangelo Ballow, Emil Frei, I. Craig Henderson
Journal: New England Journal of Medicine (1994)

Adjuvant chemotherapy is widely used for breast cancer and is known to extend survival. Some clinicians seek a greater survival benefit by increasing the intensity of the dose, whereas others lower it to diminish toxicity.
Molecular Biology and Pathogenesis of Viral Myocarditis
Authors: Mitra Esfandiarei, Bruce M. McManus
Journal: Annual Review of Pathology Mechanisms of Disease (2008)

Myocarditis is a cardiac disease associated with inflammation and injury of the myocardium. Several viruses have been associated with myocarditis in humans. However, coxsackievirus B3 is still considered the dominant etiological agent. The observed pathology in viral myocarditis is a result of cooperation or teamwork between viral processes and host immune responses at various stages of disease. Both innate and adaptive immune responses are crucial determinants of the severity of myocardial damage, and contribute to the development of chronic myocarditis and dilated cardiomyopathy following acute viral myocarditis. Advances in genomics and proteomics, and in the use of informatics and biostatistics, are allowing unbiased initial evaluations that can be the basis for testable hypotheses about virus pathogenesis and new therapies.
Warfarin in the Prevention of Stroke Associated with Nonrheumatic Atrial Fibrillation
Authors: Michael D. Ezekowitz, Samuel L. Bridgers, Kenneth E. James, Nathan H. Carliner, Cindy L. Colling, Charles C. Gornick, Heidi Krause-Steinrauf, John F. Kurtzke, Sarkis M. Nazarian, Martha J. Radford, Frederick R. Rickles, Ralph Shabetai, Daniel Deykin
Journal: New England Journal of Medicine (1992)

Nonrheumatic atrial fibrillation is common among the elderly and is associated with an increased risk of stroke. We investigated whether anticoagulation with warfarin would reduce this risk.
CDK9 inhibition induces epigenetic reprogramming revealing strategies to circumvent resistance in lymphoma
Authors: Elana Thieme, Nur Bruss, Duanchen Sun, Edward C. Dominguez, Daniel Coleman, Tingting Liu, Carly Roleder, Melissa Martinez, Krystine Garcia-Mansfield, Brian Ball, Patrick Pirrotte, Lili Wang, Zheng Xia, Alexey V. Danilov
Journal: Molecular Cancer (2023)

Abstract Diffuse large B-cell lymphoma (DLBCL) exhibits significant genetic heterogeneity which contributes to drug resistance, necessitating development of novel therapeutic approaches. Pharmacological inhibitors of cyclin-dependent kinases (CDK) demonstrated pre-clinical activity in DLBCL, however many stalled in clinical development. Here we show that AZD4573, a selective inhibitor of CDK9, restricted growth of DLBCL cells. CDK9 inhibition (CDK9i) resulted in rapid changes in the transcriptome and proteome, with downmodulation of multiple oncoproteins (eg, MYC, Mcl-1, JunB, PIM3) and deregulation of phosphoinotiside-3 kinase (PI3K) and senescence pathways. Following initial transcriptional repression due to RNAPII pausing, we observed transcriptional recovery of several oncogenes, including MYC and PIM3 . ATAC-Seq and ChIP-Seq experiments revealed that CDK9i induced epigenetic remodeling with bi-directional changes in chromatin accessibility, suppressed promoter activation and led to sustained reprograming of the super-enhancer landscape. A CRISPR library screen suggested that SE-associated genes in the Mediator complex, as well as AKT1 , confer resistance to CDK9i. Consistent with this, sgRNA-mediated knockout of MED12 sensitized cells to CDK9i. Informed by our mechanistic findings, we combined AZD4573 with either PIM kinase or PI3K inhibitors. Both combinations decreased proliferation and induced apoptosis in DLBCL and primary lymphoma cells in vitro as well as resulted in delayed tumor progression and extended survival of mice xenografted with DLBCL in vivo . Thus, CDK9i induces reprogramming of the epigenetic landscape, and super-enhancer driven recovery of select oncogenes may contribute to resistance to CDK9i. PIM and PI3K represent potential targets to circumvent resistance to CDK9i in the heterogeneous landscape of DLBCL.
Interplay Between Polymorphic Short Tandem Repeats and Gene Expression Variation in<i>Caenorhabditis elegans</i>
Authors: Gaotian Zhang, Erik C Andersen
Journal: Molecular Biology and Evolution (2023)

Short tandem repeats (STRs) have orders of magnitude higher mutation rates than single nucleotide variants (SNVs) and have been proposed to accelerate evolution in many organisms. However, only few studies have addressed the impact of STR variation on phenotypic variation at both the organismal and molecular levels. Potential driving forces underlying the high mutation rates of STRs also remain largely unknown. Here, we leverage the recently generated expression and STR variation data among wild Caenorhabditis elegans strains to conduct a genome-wide analysis of how STRs affect gene expression variation. We identify thousands of expression STRs (eSTRs) showing regulatory effects and demonstrate that they explain missing heritability beyond SNV-based expression quantitative trait loci. We illustrate specific regulatory mechanisms such as how eSTRs affect splicing sites and alternative splicing efficiency. We also show that differential expression of antioxidant genes and oxidative stresses might affect STR mutations systematically using both wild strains and mutation accumulation lines. Overall, we reveal the interplay between STRs and gene expression variation by providing novel insights into regulatory mechanisms of STRs and highlighting that oxidative stress could lead to higher STR mutation rates.